Selective serotonin reuptake inhibitors and myocardial infarction.

Abstract

HomeCirculationVol. 109, No. 3Selective Serotonin Reuptake Inhibitors and Myocardial Infarction Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBSelective Serotonin Reuptake Inhibitors and Myocardial Infarction J.-M. Le Mellédo, MD, D. Bailey, MD, PhD and G.B. Baker, PhD, DSc J.-M. Le MellédoJ.-M. Le Mellédo Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada Search for more papers by this author , D. BaileyD. Bailey Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada Search for more papers by this author and G.B. BakerG.B. Baker Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada Search for more papers by this author Originally published27 Jan 2004https://doi.org/10.1161/01.CIR.0000113707.06004.3BCirculation. 2004;109:e19To the Editor:Sauer et al1 reported a protective role in myocardial infarction of selective serotonin reuptake inhibitors (SSRIs) with high affinity for the serotonin transporter, such as paroxetine and sertraline. The rationale for this study was that depletion of platelet serotonin storage by serotonin reuptake inhibition may lead to attenuation of platelet activity and therefore decrease the risk of myocardial infarction. Discussing the lack of positive impact on cardiovascular outcome of the non-SSRI antidepressants with serotonin reuptake activity, the authors considered a balance between beneficial effects and deleterious effects, with the beneficial effects being negated by deleterious effects. We believe that such a combination of positive and negative effects also exists for SSRIs with high affinity for the serotonin transporter, even though the ultimate balance gears toward a beneficial effect. For example, paroxetine and likely sertraline substantially increase serum levels of low-density lipoprotein cholesterol,2,3 a conventional cardiovascular risk factor. Interestingly, in the Sauer et al1 report, the percentage of hypercholesterolemia appears to be greater in the group of patients taking antidepressants than in the group of subjects not using antidepressants. In the study by Serebruany et al4 quoted by the authors, more patients on SSRIs were taking lipid-lowering agents. Endothelium-derived nitric oxide (NO) is not only the major effector of vasodilatation but also inhibits platelet aggregation and adhesion. Increased endothelium NO production is usually considered to be positive from a cardiovascular point of view, whereas decreased endothelium NO production is considered to be negative. The metabolic end products of nitric oxide (NOx) are often used as a marker for endothelial NO production. We have shown that paroxetine administration increases plasma levels of NOx and normalizes initially decreased plasma levels of NOx in depressed patients (Lara et al5; W. Chrapko et al, unpublished data, 2002), which would suggest a positive cardiovascular impact of paroxetine on endothelium and platelet function.Although they did not directly measure platelet activity in their investigation, Sauer et al1 are to be commended for assessing the impact of a specific biological effect of SSRIs on cardiovascular outcome. Such studies, ideally associated with concomitant biological measurements, should lead to greater understanding of the impact of antidepressants on cardiovascular outcomes than studies without clear mechanistic hypotheses. However, on the basis of our data and those of others, the cardiovascular impact of SSRIs likely extends beyond the activity of SSRIs at the platelet serotonin transporter and includes a combination of positive and negative effects susceptible to interindividual variability.1 Sauer W, Berlin J, Kimmel SE. Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation. 2003; 108: 32–36.LinkGoogle Scholar2 Bailey D, Le Mellédo J-M. Effects of serotonin reuptake inhibitors on cholesterol levels in patients with panic disorder. J Clin Psychopharmacol. 2003; 23: 317–319.CrossrefMedlineGoogle Scholar3 Lara N, Baker G, Archer S, et al. Paroxetine-induced increased in LDL cholesterol levels. J Clin Psychiatry. 2003; 64: 1455–1459.CrossrefMedlineGoogle Scholar4 Serebruany VL, O’Connor CM, Gurbel PA. Effect of selective serotonin reuptake inhibitors on platelets in patients with coronary artery disease. Am J Cardiol. 2001; 87: 1398–1400.CrossrefMedlineGoogle Scholar5 Lara N, Archer S, Baker GB, et al. Paroxetine-induced increase in metabolic end products of nitric oxide. J Clin Psychopharmacol. 2003; 23: 408–412.MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Baskar K, Sur S, Selvaraj V and Agrawal D (2015) Functional constituents of a local serotonergic system, intrinsic to the human coronary artery smooth muscle cells, Molecular Biology Reports, 10.1007/s11033-015-3874-x, 42:8, (1295-1307), Online publication date: 1-Aug-2015. Madjid M and Casscells S (2007) Influenza vaccination as a strategy to prevent cardiovascular events The Vulnerable Plaque, Second Edition, 10.3109/9781439804537-35, (353-359), Online publication date: 13-Jun-2007. Chrapko W, Jurasz P, Radomski M, Lara N, Archer S and Le Mellédo J (2004) Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder, Biological Psychiatry, 10.1016/j.biopsych.2004.03.003, 56:2, (129-134), Online publication date: 1-Jul-2004. January 27, 2004Vol 109, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000113707.06004.3BPMID: 14744962 Originally publishedJanuary 27, 2004 PDF download Advertisement